DESCRIPTION (provided by principal investigator): This application consists of one site, complemented by three consultants, for the application "Familial Female Sexual Orientation Phenotypes" under the R21 mechanism. The long-term goal is to better understand genetic contributions to the trait of sexual orientation, one of the most important variations in human behavior, both in the realms of psychology and biology. Because sexuality is an essential part of human life, it is important to understand normal human sexual development, including sexual orientation. Female sexual orientation is strikingly different in some aspects, and understudied compared to male sexual orientation. This includes both pre-molecular approaches (e.g., family and twin studies) and especially in molecular approaches (i.e., genetic mapping). This R21 will address this knowledge gap by means of a family study to explore the relationship between female sexual orientation and associated phenotypes (fluidity, gender nonconformity, and handedness). This will guide further work with molecular approaches, especially a genome-wide association study (GWAS) that will be the focus of an ensuing R01 application. The current R21 study specific aims are: (A) to determine the most familial female sexual orientation phenotype. In a family study (N = 2,000) the following will be assessed: female sexual orientation, fluidity (i.e., fluctuation in aspects of sexual orientation), gender nonconformity, and handedness of probands (index family members) versus sexual orientation in the probands'female relatives;(B) to conduct the first family study of female sexual fluidity by comparing rates of fluidity in probands with fluidity in the probands'female relatives (by proband report, i.e., the family history method);and (C) to collect proband saliva-derived DNA samples as pilot data/biomaterials for an R01 application for a population-based case-control GWAS. Recruitment will include both 1,000 probands from Gay Pride festivals and 1,000 probands from general community festivals, resulting in ~1,000 lesbian or bisexual and ~1,000 heterosexual female probands. These probands complete questionnaires about their sexual orientation, fluidity, gender nonconformity, and handedness. The will also provide information on sexual orientation and fluidity of their female first- and second-degree relatives (expecting about 9 such relatives per proband). On a subset of ~500 probands, questionnaire data will also be collected directly from their relatives by means of the same anonymous questionnaire online to validate the information obtained by the family history method. Preliminary analyses suggest that for the proposed sample size, these aims can be achieved with high statistical power. PUBLIC HEALTH RELEVANCE: Contributions to the development of sexual orientation, one the most important variations in human behavior, are largely unknown, though more extensively studied in males compared to females. Because sexuality is an essential part of human life - for individuals and society - it is important to understand normal human sexual development, including sexual orientation. Furthermore, factual information about sexuality can help prevent distorted and hostile views.